The kallikrein-kinin system may participate in the regulation of renal blood flow and sodium excretion. The purpose of this project is to define an intrarenal role for the kallikrein-kinin system in the regulation of sodium excretion, renal vascular resistance and systemic blood pressure. In chloralose-anesthetized dogs we will explore the effects of various experimental interventions (sodium-load, renal ischemia, intrarenal infusions of bradykinin, angiotensin, norepinephrine, etc.) on renal blood flow, perfusion pressure, glomerular filtration rate, urinary excretion of sodium and potassium, and relate them to changes in the kinin and kininogen levels in renal venous blood, kallikrein excretion in urine and kallikrein activity in lymph. Having defined the experimental conditions which alter the intrarenal activity of the kallikrein-kinin system, we will attempt to establish a cause-effect relationship by studying the effects of factors which might enhance (bradykinin potentiating peptides) or attenuate (carboxypeptidase B) the renal actions of kinins under circumstances in which the activity of the kallikrein-kinin system of the kidney is altered. Possible interactions between renin and kallikrein will also be investigated by relating simultaneous measurements of plasma renin, blood kinins, renin and kallikrein content of the kidney under acute and chronic experimental conditions (renal ischemia, mineralocorticoid treatment, etc.). In addition, we will relate the natriuretic and hemodynamic responses to intrarenal infusions of bradykinin, to the levels of kinins in renal venous blood and to changes in the survival of the peptide on passage across the kidney. Finally, possible interrelationships between kininases and angiotensin II converting enzyme in the kidney will be examined. We expect, thereby, to define more fully, possible hormonal factors which participate in the regulation of the renal circulation and sodium excretion.